Global anthropogenic flows of nitrogen (N) and phosphorus (P) have exceeded planetary boundaries with significant implications for pollution of the freshwater resources in the world. Understanding the global patterns and drivers of N and P concentrations and their ratios in the lakes could help design more effective management and remediation strategies to mitigate the impacts of eutrophication. While a suite of drivers are associated with the sources of nutrients, their transport and internal processes that control concentrations of N and P in the lakes, much less is known about the relative importance of different drivers in explaining spatial variations of lake nutrients and ratios. In this study, we compared N and P concentrations and their ratios in the lakes across China and Europe and examined the differences of dominant environmental and social drivers on lake nutrients. Our comparison showed that total nitrogen (TN) and total phosphorus (TP) concentrations were much higher in the lakes in China compared to those in Europe (i.e., TN: 1.13 mg/L in China vs. 0.64 mg/L in Europe; TP: 35.83 μg/L in China vs. 19.38 μg/L in Europe, the median value). However, lake N/P ratios for both regions were not statistically different. Concentrations of TN and TP showed decoupling in both regions, with the majority of lakes having high N/P mass ratios when evaluated by the commonly accepted threshold of 23 (i.e., 61% in China and 68% in Europe), indicating that phytoplankton are more P limited relative to N. Agricultural activity in the lake catchment is an important predictor for both nutrient concentrations and their ratio in Europe. This reflects successful investments in infrastructure and policy prescriptions in addressing point sources of pollution. In comparison, lake depth and water residence time are important in the decoupling of N and P concentrations in China. The regional difference between the dominant drivers can provide important insights into development of effective water pollution control measures. It is necessary for policy makers and water resource managers to be aware of large-scale imbalance of nutrients in lake due to the potential environmental consequences. A set of spatially flexible policies for water quality controls would be beneficial for sustaining the ecological integrity and future health of lakes.